Gay Steffen

Group Leader

Prof. Dr. Steffen Gay

Name of the Institution

Center of Experimental Rheumatology
Department of Rheumatology
UniversityHospital Zurich

Street

Gloriastrasse 25

City

CH-8091 Zürich

Phone

+41-44-255 57 37

Fax

+41-44-255 41 70

E-mail

Group Members Experimental Rheumatology

Renate E. Gay MD, Professor, renate.gay@usz.ch
Michel Neidhart PhD, Professor, Oberassistent, michel.neidhart@usz.ch
Oliver Distler MD, Professor, Leitender Arzt, oliver.distler@usz.ch
Adrian Ciurea MD, PD, adrian.ciurea@usz.ch

Borbala Aradi, MD, Postdoc, borbala.aradi@usz.ch
Mojca Frank, MD, PhD, Postdoc, mojca.frank@usz.ch
Suzana Jordan, PhD, Postdoc, suzana.jordan@usz.ch
Astrid Jüngel, PhD, PD, astrid.juengel@usz.ch
Emmanuel Karouzakis, PhD, Postdoc, emmanuel.karouzakis@usz.ch
Kerstin Klein, PhD, Postdoc, kerstin.klein@usz.ch
Christoph Kolling, MD, Postdoc, Christoph.Kolling@kws.ch
Britta Maurer, MD, Senior-Postdoc, britta.maurer@usz.ch
Caroline Ospelt, MD, PhD, caroline.ospelt@usz.ch
Lenka Plestilova, MD, Postdoc, lenka.plestilova@usz.ch

Peter Künzler, MSc, Lab Manager, peter.kuenzler@usz.ch
Maria Comazzi, Histology Technician, maria.comazzi@usz.ch
Benvinda Henriques, Lab support, benvinda.henriques@usz.ch
Christoph Rudolf, Accounting, christoph.rudolf@usz.ch
Fabienne Wullschleger, Accounting, fabienne.wullschleger@usz.ch
Tiffany Cheok, Secretary, tiffany.cheok@usz.ch
Georgina Mathis-Pairo, Secretary, georgina.mathis@usz.ch

Group Members Research of Systemic Autoimmune Diseases

Distler Oliver MD, Professor, oliver.distler@usz.ch
Group leader Research of Systemic Autoimmune Diseases

Kania Gabriela, PD Dr., Senior Scientist, gabriela.kania@usz.ch
Maurer Britta MD, Dr., Consultant Rheumatologist and Senior Scientist, britta.maurer@usz.ch

Jüngel Astrid, PD Dr. rer. nat., Senior Scientist, astrid.juengel@usz.ch

Jordan Suzana, Dr., Clinical Investigator, suzanna.jordan@usz.ch
Dobrota Rucsandra MD, Clinical Science Research Fellow, rucsandra.dobrota@usz.ch
Horai Yoshiro, Research Fellow, yoshiro.horai@usz.ch
Zhongning Guo, Dr., Research Technician, zhongning.guo@usz.ch

Kozlova Anastasiia, PhD student, anastasiia.kozlova@usz.ch
Pachera Elena, PhD student, elena.pachera@usz.ch
Renoux Florian, PhD student, florian.renoux@usz.ch
Rudnik Michal, PhD student, michal.rudnik@usz.ch
Schniering Janine, PhD student, janine.schniering@usz.ch
Stellato Mara, PhD student, mara.stellato@usz.ch

Schneider Nicole, Administration, nicole.schneider@usz.ch

Current fields of research Experimental Rheumatology

Epigenetic modifications in rheumatic and cardiovascular diseases including methylation, acetylation, sumoylation and microRNA, represent the major focus of our current research.

The molecular and cellular basis of joint destruction in rheumatoid arthritis, osteoarthritis and ankylosing spondylitis, involves especially the search for novel genes and their signaling pathways (“Functional Genomics”).

The laboratory explores the molecular and cellular mechanisms by studying the processes of synovial adhesion to cartilage and bone, the activation of synovial cells to invade and the cellular interactions with cells of the immune system. The role of microparticles and modulating gene expression are another focus of our interest.

Suppressive subtractive hybridization and arrays are used to establish cDNA libraries of genes which are induced by various stimuli, including signaling via cytokine receptors and TOLL-like receptors.

Somatic gene transfer is applied to inhibit synovial cell-mediated cartilage destruction in the SCID mouse model engrafted with normal human cartilage and rheumatoid synovial tissues or isolated cells. Anti-sense constructs, ribozymes , siRNA and antagomirs are used to identify specific targets for future therapeutical interventions. The model is further used to explore the effect of novel drugs from the pharmaceutical industry.

In close cooperation with the Department of Cardiology at the University Hospital of Zürich, we are studying the endothelial function in both rheumatic and cardiovascular patients. Novel investigations on fresh thrombi retrieved from myocardial infarcted patients explore the role of inflammation in the acute coronary syndrome.

A new clinical Research Program has been developed entitled “Molecular Analysis of Gene Expression modulated by Novel Drug Therapies” to study the molecular effects of drugs on individual cells. By evaluating most comprehensively these changes, novel modes of action as well as unwanted side effects can be discovered to develop safer therapeutics.

Current fields of research Systemic Autoimmune Diseases

We are focusing on two connective tissue diseases, systemic sclerosis and inflammatory myopathy. It is one of the internationally leading scleroderma research centers. It has research programs both in clinical research as well as in basic science research.

Systemic sclerosis (SSc) is an autoimmune disease characterized by widespread vasculopathy, inflammation and fibrosis of skin and internal organs. This leads to thickening of the skin as well as irreversible functional impairment of organ function. However the etiology of SSc is unclear and the molecular mechanisms underlying the disease are poorly understood. In several independent but cooperative projects, we aim to determine molecular mechanisms that drive the onset and progression of fibrosis in SSc skin or internal organs.

The term inflammatory myopathy (myositis) comprises a group of heterogeneous autoimmune diseases which are characterized by the presence of an inflammatory infiltrate within the muscle tissue. The skin, the musculoskeletal system, but also internal organs such as lung, heart, or gastrointestinal tract might also be affected. Thus, those orphan diseases have a high morbidity and a significantly increased mortality. Current research efforts in basic science are aimed at the identification of molecular key players of disease pathogenesis as potential therapeutic targets.

Special Techniques and Equipment

In vitro assays and the SCID mouse model of cartilage destruction
Ex vivo gene transfer to synovial cells
Suppressive subtractive hybridization and gene arrays

Education and Training

We have established a molecular biology training course, twice a year, to train new international research fellows in cloning, sequencing, cell-culture, cell-sorting (FACS), TaqMan Real Time PCR, primer design, in situ PCR, in situ hybridization , analysis of acetylation, methylation and miRNAs and immunohistology.

Selected publications

  1. Iwamoto N, Vettori S, Maurer B, Brock M, Pachera E, Jüngel A, Calcagni M, Gay RE, Whitfield ML, Distler JH, Gay S, Distler O. Downregulation of miR-193b in systemic sclerosis regulates the proliferative vasculopathy by urokinase-type plasminogen activator expression. Ann Rheum Dis. 2014 [Epub ahead of print]
    IF: 10.377
  2. Kurinna S, Schäfer M, Ostano P, Karouzakis E, Chiorino G, Bloch W, Bachmann A, Gay S, Garrod D, Lefort K, Dotto GP, Beer HD, Werner S. A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes. Nat Commun 5:5099, 2014
    IF: 10.742
  3. Neidhart M, Karouzakis E, Jüngel A, Gay RE, Gay S. Inhibition of spermidine/spermine N1-acetyltransferase (SSAT1) activity - a new therapeutical concept in rheumatoid arthritis. Arthritis Rheumatol 66:1723-1733, 2014
    IF: 7.4477
  4. Shah N, Hülsmeier AJ, Hochhold N, Neidhart M, Gay S, Hennet T. Exposure to mimivirus collagen promotes arthritis. J Virol 88:838-45, 2014
    IF:5.076
  5. Brock M, Samillan VJ, Trenkmann M, Schwarzwald C, Ulrich S, Gay RE, Gassmann M, Ostergaard L, Gay S, Speich R, Huber LC. AntagomiR directed against miR-20a restores functional BMPR2 signalling and prevents vascular remodelling in hypoxia-induced pulmonary hypertension. Eur Heart J 35:3203-11, 2014
    IF:10.446
  6. Maurer B, Graf N, Michel BA, Müller-Ladner U, Czirják L, Denton C, Tyndall A, Baron M, Metzig C, Lanius V, Khanna D, Distler O, and EUSTAR co-authors. Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database. Ann Rheum Dis.2014. [Epub ahead of print]
    IF:10.377
  7. Jordan S, Distler JHW, Maurer B, Huscher D, van Laar JM, Allanore Y, Distler O. Effects and safety of Rituximab in Systemic Sclerosis: An analysis from the European Scleroderma Trial and Research group (EUSTAR). Ann Rheum Dis 2014 [Epub ahead of print]
    IF:10.377
  8. Frank S, Peters MA, Wehmeyer C, Strietholt S, Koers-Wunrau C, Bertrand J, Heitzmann M, Hillmann A, Sherwood J, Seyfert C, Gay S, Pap T. Regulation of matrixmetalloproteinase-3 and matrix-metalloproteinase-13 by SUMO-2/3 through the transcription factor NF-κB. Ann Rheum Dis 72:1874-1881, 2013
    IF: 9.082
  9. Maurer B, Distler A, Suliman YA, Gay RE, Michel BA, Gay S, Distler JHW, Distler O. Vascular endothelial growth factor aggravates fibrosis and vasculopathy in experimental models of systemic sclerosis. Ann Rheum Dis Ann Rheum Dis 73:1880-7, 2014 [Epub 2013]
    IF:9.111
  10. Maurer B, Distler A, Dees C, Khan K, Denton CP, Abraham D, Gay RE, Michel BA, Gay S, HW Distler J, Distler O. Levels of target activation predict antifibrotic responses to tyrosine kinase inhibitors. Ann Rheum Dis. 2013;72(12):2039-46
    IF:9.111
  11. Gerlag DM, Raza K, van Baarsen LG, Brouwer E, Buckley CD, Burmester GR, Gabay C, Catrina AI, Cope AP, Cornelis F, Dahlqvist SR, Emery P, Eyre S, Finckh A, Gay S, Hazes JM, van der Helm-van Mil A, Huizinga TW, Klareskog L, Kvien TK, Lewis C, Machold KP, Rönnelid J, Schaardenburg DV, Schett G, Smolen JS, Thomas S, Worthington J, Tak PP. EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid Arthritis. Ann Rheum Dis 71:638-41, 2012
    IF: 10.377
  12. Nikitopoulou I, Oikonomou N, Karouzakis E, Sevastou I, Nikolaidou-Katsaridou N, Zhao Z, Mersinias V, Armaka M, Xu Y, Masu M, Mills GB, Gay S, Kollias G, Aidinis V. Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis. J Exp Med 209:925-33, 2012
    IF: IF: 13.853
  13. Maurer B, Reich N, Juengel A, Kriegsmann J, Gay RE, Schett G, Michel BA, Gay S, Distler JH, Distler O. Fra-2 transgenic mice as a novel model of pulmonary hypertension associated with systemic sclerosis. Ann Rheum Dis. 2012;71(8):1382-7
    IF:10.377
  14. Kurowska-Stolarska M, Alivernini S, Ballantine LE, Asquith DL, Millar NL, Gilchrist DS, Reilly J, Ierna M, Fraser AR, Stolarski B, McSharry C, Hueber AJ, Baxter D, Hunter J, Gay S, Liew FY, McInnes IB. MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci USA 108(27):11193-8, 2011
    IF: 9.771
  15. Dees C, Akhmetshina A, Zerr P, Reich N, Palumbo K, Horn A, Jüngel A, Beyer C, Krönke G, Zwerina J, Reiter R, Alenina N, Maroteaux L, Gay S, Schett G, Distler O, Distler JH. Platelet-derived serotonin links vascular disease and tissue fibrosis. J Exp Med 208(5):961-72, 2011
    IF: 14.776
  16. Maurer B, Stanczyk J, Jüngel A, Akhmetshina A, Trenkmann M, Brock M, Kowal-Bielecka O, Gay RE, Michel BA, Distler JHW, Gay S, Distler O. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum. 2010;62(6):1733-43
    IF: 8.435
  17. Reich N, Maurer B, Akhmetshina A, Venalis P, Dees C, Zerr P, Palumbo K, Zwerina J, Nevskaja T, Gay S, Distler O, Schett G, Distler JH. The transcription factor Fra-2 regulates the production of extracellular matrix in systemic sclerosis. Arthritis Rheum. 2010;62(1):280-90
    IF: 8.435
  18. Maurer B, Busch N, Jüngel A, Pileckyte M, Gay RE, Michel BA, Schett G, Gay S, Distler J, Distler O. Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis. Circulation. 2009;120(23):2367-76
    IF: 14.429

Funding

EC Masterswitch 2008-2013
IAR (Institute for Arthritis Research) 2010-2016
EC BTCure 2011-2016
EC FP7-People-2011 Networks for Initial Training (ITN) Marie Curie Osteoimmune 2012-2016
EC Health 2012 Innovation Euro-TEAM 2012-2016
DeSscipher
Foreign Government Exchange Agencies
Research Foundations
Industry

Link to Research Database “Forschungsdatenbank” of the University